ASP Scan (Weekly) for Dec 21, 2018

Rapid meningitis tests
Novel pneumonia antibiotic
Sparse antibiotic use and resistance
Metronidazole for mild C diff
Drop in children's antibiotic use
C difficile in toilet water

Ethiopian study shows potential of rapid diagnostic test for meningitis

Ethiopian researchers report that the introduction of a rapid molecular diagnostic test at a teaching hospital resulted in the first diagnosis of viral meningitis in routine clinical practice in Ethiopia. The study was published yesterday in BMC Infectious Diseases.

In the single-center study, cerebrospinal fluid (CSF) samples from patients with suspected meningitis at Jimma University Specialized Hospital were analyzed using a multiplex, polymerase chain reaction (PCR)-based system and conventional microbiologic methods. The aim of the study was to investigate which infectious agents were responsible for meningitis in a region of Ethiopia where treatment decisions are usually based on clinical findings alone and bacterial meningitis is frequently diagnosed, resulting in antibiotic overuse

Of the 218 CSF samples collected, microorganisms were detected by PCR in 21 (10%). The rates were 4% in neonates, 14% in pediatric patients, and 18% in adults. By comparison, conventional testing detected a microorganism in only five patients.

Virus was detected in 57% of the PCR-positive samples, bacteria in 33%, and fungi in 10%. The vast majority (90%) of patients, however, still received more than one antibiotic for the treatment of the meningitis episode, and there was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without. The authors of the study suggest this could be caused by a lack of clinical treatment guidelines or poor communication of test results to clinicians.

The authors conclude that while cost is a limitation to sustained use of such automated diagnostic systems in a country like Ethiopia, the study illustrates how improved diagnostics, together with development of treatment guidelines, could reduce antibiotic use in meningitis patients.
Dec 20 BMC Infect Dis study


Company submits New Drug Applications to FDA for pneumonia antibiotic

Drug company Nabriva Therapeutics of Dublin yesterday announced it has submitted two New Drug Applications (NDAs) to the US Food and Drug Administration (FDA) for the oral and intravenous (IV) formulations of lefamulin, a first-in-class, semi-synthetic pleuromutilin antibiotic that is designed for treating community-acquired bacterial pneumonia (CABP).

"The submission of the lefamulin NDAs marks another major milestone for Nabriva Therapeutics, demonstrating our commitment to develop novel anti-infective agents that address the urgent, unmet medical need faced by patients with serious infections," said Jennifer Schranz, MD, Nabriva's chief medical officer, in a company news release. "Lefamulin has the potential to provide a much-needed monotherapy treatment option for adults with CABP in both the hospital and ambulatory care settings."

The company said the two NDAs are supported by two phase 3 clinical trials—known as LEAP 1 and LEAP 2—that evaluated the safety and efficacy of IV and oral lefamulin compared with moxifloxacin in adults with CABP, including the option to switch from IV to oral administration and a short course of oral treatment with lefamulin. "In both LEAP 1 and LEAP 2, lefamulin was demonstrated to be non-inferior to moxifloxacin, and met both the FDA and European Medicines Agency (EMA) primary and secondary efficacy endpoints for the treatment of CABP," the company said.

Lefamulin was also generally well tolerated in the trials. Nabriva plans to submit a marketing authorization application for lefamulin in Europe in the first quarter of 2019.
Dec 20 Nabriva news release


Study finds link between occasional antibiotic use and resistance

Originally published by CIDRAP News Dec 19

Antibiotic resistance in the United States appears to be more closely linked to occasional antibiotic use by many people rather than heavy use by few people, and resistance to certain antibiotics is higher in areas where they are used more often, according to a comprehensive study yesterday in eLife.

US and Canadian experts analyzed 99.8 million outpatient pharmacy antibiotic prescription fills among 108 million unique people (about 20% of the US population) from 2011 through 2014 using the MarketScan database. They noted that, in 2011, 34% of the people took an antibiotic, but 10% of them received 57% of all prescriptions, which is similar to previously published UK data. The distribution varied by population but was similar across all 4 years.

The researchers also examined data from 2012 to 2015 from ResistanceOpen, which tracks antibiotic resistance across the country. To correlate antibiotic use for a particular drug with rates of antibiotic resistance against that drug, the researchers looked at 72 pairs of antibiotics and bacteria.

The investigators found that the more a particular antibiotic was used, the greater the resistance. For instance, in states that use more quinolones, more infections caused by Escherichia coli tend to be resistant to quinolones.

When comparing occasional, low-intensity antibiotic use by many people to intense use by a few people, however, they found that occasional, low-intensity use was more closely associated with rates of resistance.

"Our findings suggest that combatting inappropriate antibiotic use among people who don't take many antibiotics may be just as important, or more important, to fighting resistance than focusing on high-intensity users," said lead author Scott Olesen, PhD, a postdoctoral fellow at the Harvard TH Chan School of Public Health, in a Harvard news release. "More antibiotic use generally means more antibiotic resistance, but it seems like the number of people taking antibiotics might matter more than the amount they're taking."
Dec 18 eLife abstract
Dec 18 Harvard news release


VA study: Metronidazole still appropriate for mild C diff in select patients

Originally published by CIDRAP News Dec 19

A study yesterday in Clinical Infectious Diseases suggests metronidazole may be considered for treating initially mild Clostridioides difficile infection (CDI) in patients 65 years old or younger.

Until recently, metronidazole was recommended as the first-line treatment option for mild-to-moderate CDI, but updated guidelines now recommend vancomycin for initial non-severe CDI. Despite these guidelines, some reports still recommend that metronidazole be considered in certain patients who have mild CDI and a low risk for disease complications. But limited data exist to identify these patients.

To answer the question of which patients can still be treated with metronidazole, researchers with the Providence Veterans Affairs (VA) Medical Center conducted a two-stage analysis in a cohort of veterans from 125 VA centers with a first episode of mild CDI. The first stage was a predictive analysis regarding which patients treated with metronidazole have successful outcomes, and the second stage compared clinical outcomes in patients treated with metronidazole versus those treated with vancomycin.

Among 3,656 patients treated with metronidazole, the researchers identified 3,282 patients with success and 374 patients without success. Younger age was the only independent predictor of success, with patients 65 and younger associated with an odds of success 1.63 times higher (95% confidence interval [CI], 1.29 to 2.06) than those over 65. Among 115 propensity-score matched pairs of patients under 65, no significant differences were observed between metronidazole and vancomycin for all-cause mortality (hazard ratio [HR], 0.29; 95% CI, 0.06 to 1.38), CDI recurrence (HR, 0.62; 95% CI, 0.26 to 1.49), or treatment failure (HR, 0.50; 95% CI, 0.23 to 1.07).

The authors of the study say continued work is needed to investigate which severity criteria are most useful in defining mild disease that can be successfully treated with metronidazole.
Dec 18 Clin Infect Dis abstract


Study finds substantial declines in children's outpatient antibiotic use

Originally published by CIDRAP News Dec 17

Data from three large health plans shows a substantial decline in outpatient antibiotic use in children from 2010 through 2014, according to a study today in Pediatrics.

For the study, researchers analyzed pharmacy claims data from three commercial health plans (Plans A, B, and C) in three different regions of the United States, covering children between 3 months and 18 years of age. The same research team has been monitoring the data since 2000, and a previous study had found that the substantial downward trend in antibiotic use among children since 2000 had begun to plateau by 2009-2010. To determine whether antibiotic use has continued to decline or remain stable, the researchers calculated population-based antibiotic-dispensing rates for the three health plans for each study year from 2000 through 2014.

The results showed clear and substantial additional declines in antibiotic use among children in all age groups in the three health plans from 2009-2010 through 2013-2014. Looking at 2000-2001 through 2013-2014, the researchers found overall declines across all three health plans of 40% to 50% among children under the age of 6, who have the highest rates of antibiotic use of any age group. Declines in the range of 20% to 40% were observed in older children and adolescents. Consistent with the findings of the previous studies, antibiotic prescribing rates were markedly lower in Plan B, an integrated delivery health system plan located in the Mountain West.

The results also showed that the fraction of antibiotic prescribing associated with diagnoses of viral illnesses decreased in all age groups, and that use of second-generation macrolides and cephalosporins—neither of which are considered first-line treatment for common pediatric infections—declined from 2009-2010 through 2013-2014, after marked increases the decade before.

Though they acknowledge that a substantial fraction of antibiotic prescribing in all age groups remains unnecessary and that further reductions are possible, the authors of the study conclude, "We believe that child health professionals can be justifiably proud of the major change in practice that has occurred in outpatient prescribing of antibiotics."
Dec 17 Pediatrics study


Study shows C diff spores persist in toilet water and on bathroom surfaces

Originally published by CIDRAP News Dec 17

A new study by researchers from the University of Oklahoma College of Public Health suggests that toilets may be a persistent source of environmental C difficile contamination. The findings appear in the American Journal of Infection Control.

In the experimental study, the researchers seeded a flushometer-style toilet in a sealed chamber with a non-pathogenic strain of C difficile spores. The toilet was then flushed 24 times, and the researchers collected post-flush bowl water samples to measure C difficile in the toilet water. They also evaluated large droplets on toilet and bathroom surfaces and air samples to measure environmental contamination and the presence of bacteria in aerosol from the toilet plume.

The researchers captured C difficile spores in all post-flush water samples in all trials, indicating persistent contamination even after 24 flushes. In addition, C difficile spores detected in large droplets on toilet and bathroom surfaces accumulated over the 24-flush period. Droplet nuclei spore bioaerosol was produced over at least 12 flushes.

"These results demonstrate that toilets contaminated with C difficile spores will produce numerous large droplet and droplet nuclei bioaerosols that can contaminate surfaces close to and distant from the source," the authors of the study write. "Further, the microbial contamination will persist in the bowl water for many flushes after initial contamination and produce bioaerosol with each flush."

The authors say the results have significant implications for public access environments where people shedding C difficile, or other gastrointestinal pathogens, may contaminate a toilet that is subsequently used by other people. 
Dec 14 Am J Infect Control study

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